Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 100, Issue 9, Pages 3682-3695Publisher
WILEY
DOI: 10.1002/jps.22592
Keywords
albumin; antioxidants; metabolic clearance; free radicals; protein binding; membrane transport; organic anion transporters; pharmacokinetics; protein binding; renal transport
Funding
- Grants-in-Aid for Scientific Research [21590054] Funding Source: KAKEN
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Protein-bound uremic toxins, such as indoxyl sulfate, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, p-cresyl sulfate, hippuric acid, and indoleacetic acid, have been the subjects of extensive investigations. In this review, we summarized the recent works providing the new insight on the pharmacokinetics and redox properties of these uremic toxins. They have a common characteristic of being difficult to remove by conventional dialysis because they all bind tightly to serum albumin. They are transported via organic anion transporters to various tissues, and accumulate not only in the kidney but also in other tissues including vascular endothelial cells, smooth muscle cells, osteoblasts, and the central nervous system. Accumulated uremic toxins alter nonrenal drug clearance. Intracellular accumulated uremic toxins have been linked to the induction of oxidative stress and the stimulation of proinflammatory cytokines through the production of reactive oxygen species, which play a role in the progression of chronic kidney disease and the development of complications. Unfortunately, despite the massive amount of information on the undesirable effects of uremic toxins, methods for improving the detoxification of these toxins appear to be lacking. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3682-3695, 2011
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